Memory is a complex process, one that we have only just begun to understand. Research hints that it might be possible for histone modification to degrade memory if we don’t get enough sleep or that certain epigenetic anti-cancer drugs known as HDAC inhibitors could sharpen memory. RNA methylation is an epigenetic mechanism that has been recently gained a lot of attention in the field of epigenetics. Now, scientists have discovered that the epigenetic mark found on RNA, called m6A, or N6-methyladenosine, could help strengthen memory formation.
Timothy Bredy, associate professor of neurobiology & behavior from University of California, Irvine (UCI), led a team of researchers from UCI and the University of Queensland to investigate RNA methylation and memory. The group recently published their study in the Journal of Neuroscience. Their results indicated that RNA methylation may play a role in forming long-term memories. The epigenetic modification known as RNA methylation is defined as the addition of a methyl group to RNA, forming m6A. Modifications that occur to RNA can impact how it functions in a cell, even though researchers aren’t certain yet whether m6A is dynamically regulated by experience.
In this study, the team found that the enzyme that removes methyl groups from RNA, known as RNA demethylase, was linked to memory in male mice. Specifically, a reduction in the levels of RNA demethylase in the brain was connected to an upregulation of m6A in the brain and a boost in the formation of memories.
Jocelyn Widagdo, co-lead author and postdoctoral fellow from the Queensland Brain Institute in Australia, explained, “By genetically silencing an enzyme in a specific region of the brain involved in memory and adaptive behavior, we saw much better memory recall in mice.”
The team set out to see if there might be a role that RNA methylation plays in memory formation, looking at an area of the brain in mice known as the medial prefrontal cortex (mPFC). The mPFC has been connected to the encoding of fear memory in previous investigations. Using a technique called methylated RNA immunoprecipitation sequencing (MeRIP-seq), the researchers assessed genome-wide RNA methylation in brain tissue after the mice had been trained to do a learning task. They found that m6A was upregulated, which was linked to enhanced consolidation of memory.
“Our findings show that memory processing is not just influenced by epigenetic control over our DNA but also occur at the level of RNA, variations in which act like a messenger in our cells,” said Bredy. “m6A shows enormous potential because the process can rapidly fine-tune our gene function and expression, which is often impaired in a variety of neurological disorders.”
Because this research is preliminary, the group suggests that additional studies should be conducted to learn about the role of m6A, especially in regard to other forms of learning and whether the process is disrupted in disorders related to memory, such as phobia or post-traumatic stress disorder.
Source: Widagdo, J., Zhao, Q-Y., Kempen, M-J., Tan, M.C., Ratnu, V.S., Wei, W., Leighton, L., Spadaro, P.A., Edson, J., Anggono, V., Bredy, T.W. (2016). Experience-Dependent Accumulation of N6-Methyladenosine in the Prefrontal Cortex Is Associated with Memory Processes in Mice. Journal of Neuroscience, 36(25): 6771.
Reference: University of California, Irvine. UCI, Queensland scientists identify new switch to boost memory. 22 Jun 2016. Web.